Potassium Carbonate → HCID 178461159, compound

HRID 1510152Notes

Reaction equation

HRID 1510152 reaction equation
[F:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[C@:13]2([CH2:18][CH2:17][NH:16][C@@H:15]([CH3:19])[CH2:14]2)[N:12]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[C:11](=[O:27])[N:10]=1.F[C@H]1CCCC[C@@H]1NC1[C@]2(CCN[C@@H](C)C2)N([C:47]2[CH:52]=[CH:51][CH:50]=[C:49](F)C=2)C(=O)N=1.C([O-])([O-])=O.[K+].[K+].BrCC1CCC1>CN(C=O)C.O>[CH:50]1([CH2:49][N:16]2[CH2:17][CH2:18][C@@:13]3([N:12]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=4)[C:11](=[O:27])[N:10]=[C:9]3[NH:8][C@@H:3]3[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]3[F:1])[CH2:14][C@@H:15]2[CH3:19])[CH2:51][CH2:52][CH2:47]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 178461161HCID 178461161, compoundHCID 178461162HCID 178461162, compound

Product 1

HCID 178461159HCID 178461159, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution containing 55 mg (0.15 mmol) of (5R,7S)-4-{[(1R,2R)-2-fluorocyclohexyl]amino}-1-(3-fluorophenyl)-7-methyl-1,3,8-triazaspiro[4.5]dec-3-en-2-one and (5R,7S)-4-{[(1S,2S)-2-fluorocyclohexyl]amino}-1-(3-fluorophenyl)-7-methyl-1,3,8-triazaspiro[4.5]dec-3-en-2-one in DMF (1.5 mL) was added powdered K2CO3 (81 mg, 0.58 mmol) and bromomethylcyclobutane (22 mg (0.15 mmol). The solution was heated to 60° C. overnight. The reaction was diluted with water (1.5 mL) and extracted three times with EtOAc. The combined organics were dried over MgSO4, filtered and concentrated then chromatographed using 100% EtOAc to give the desired product which was further purified on a Waters automated system affixed with a Chiralpak AD 5 cm×50 cm cartridge eluting at 80 mL/min with isocratic 20% ethyl alcohol in hexanes with no modifier. The second peak was the product. The salt could be formed as described for the examples in Table 5.

Workup

  1. extractionextracted three times with EtOAc
  2. dry with materialThe combined organics were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthen chromatographed

Sources & evidence

ORD record
ord-d7f3e70cf4474f4cbd2460f183ec2e85
Source dataset
uspto-grants-2012_07
Patent number
US08211904B2

Reaction notes

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